Neck metastasis is the most significant clinical factor responsible for death from oral squamous cell carcinoma (SCC). The metastatic behavior of oral SCC is highly variable and there is not a clinical, histologic or molecular method to determine which oral SCCs will metastasize. We propose to find molecular markers in oral SCC that predict metastasis. We will pursue a comprehensive step-wise approach designed to converge on a small set of informative markers that discriminate between oral cavity SCCs with and without metastatic potential. Aim 1 is designed to use array CGH to identify genomic copy number aberrations associated with non-metastatic and metastatic oral SCCs. In Aim 2 we will analyze candidate genes in the regions of recurrent copy number aberrations identified in Aim 1. We will also evaluate the oral SCCs for genes that have been established in the literature to have a role in oral SCC metastasis. The results of Aims 1 and 2 will provide us with a composite molecular marker (copy number aberrations, gene expression changes and protein levels) that can distinguish between oral SCCs with and without metastatic potential. The molecular markers will then be tested on an independent set of oral SCCs in Aim 3. Together, we anticipate that these studies will establish and validate a predictive molecular marker for oral SCC metastasis. The Public Health relevance of this project is that successful identification of molecular markers predictive of oral cancer metastasis would profoundly decrease the morbidity associated with radiation therapy, improve tumor control rates and increase patients' quality of life. [unreadable] [unreadable] [unreadable]